+Open data
-Basic information
Entry | Database: PDB / ID: 7keu | ||||||
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Title | Cryo-EM structure of the Caspase-1-CARD:ASC-CARD octamer | ||||||
Components |
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Keywords | IMMUNE SYSTEM / ASC / Apoptosis-associated speck-like protein containing a CARD / PYCARD / caspase-1 / cryo-EM / helical filament / octamer | ||||||
Function / homology | Function and homology information Pyrin domain binding / NLRP6 inflammasome complex / myosin I binding / positive regulation of antigen processing and presentation of peptide antigen via MHC class II / myeloid dendritic cell activation involved in immune response / regulation of intrinsic apoptotic signaling pathway / caspase-1 / protease inhibitor complex / myeloid dendritic cell activation / IkappaB kinase complex ...Pyrin domain binding / NLRP6 inflammasome complex / myosin I binding / positive regulation of antigen processing and presentation of peptide antigen via MHC class II / myeloid dendritic cell activation involved in immune response / regulation of intrinsic apoptotic signaling pathway / caspase-1 / protease inhibitor complex / myeloid dendritic cell activation / IkappaB kinase complex / AIM2 inflammasome complex assembly / The AIM2 inflammasome / macropinocytosis / The IPAF inflammasome / AIM2 inflammasome complex / IPAF inflammasome complex / icosanoid biosynthetic process / interleukin-6 receptor binding / NLRP1 inflammasome complex / cytokine precursor processing / canonical inflammasome complex / NLRP3 inflammasome complex assembly / positive regulation of interleukin-18 production / positive regulation of adaptive immune response / BMP receptor binding / NLRP3 inflammasome complex / CARD domain binding / caspase binding / negative regulation of protein serine/threonine kinase activity / negative regulation of interferon-beta production / CLEC7A/inflammasome pathway / positive regulation of cysteine-type endopeptidase activity / positive regulation of tumor necrosis factor-mediated signaling pathway / regulation of tumor necrosis factor-mediated signaling pathway / Interleukin-1 processing / osmosensory signaling pathway / positive regulation of extrinsic apoptotic signaling pathway / Interleukin-37 signaling / positive regulation of macrophage cytokine production / pattern recognition receptor signaling pathway / : / positive regulation of actin filament polymerization / negative regulation of NF-kappaB transcription factor activity / tropomyosin binding / signaling receptor ligand precursor processing / positive regulation of activated T cell proliferation / TP53 Regulates Transcription of Caspase Activators and Caspases / pyroptotic inflammatory response / cysteine-type endopeptidase activator activity involved in apoptotic process / positive regulation of release of cytochrome c from mitochondria / positive regulation of cysteine-type endopeptidase activity involved in apoptotic process / positive regulation of interleukin-10 production / protein autoprocessing / The NLRP3 inflammasome / protein maturation / intrinsic apoptotic signaling pathway by p53 class mediator / negative regulation of cytokine production involved in inflammatory response / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of T cell migration / cellular response to interleukin-1 / Pyroptosis / Purinergic signaling in leishmaniasis infection / positive regulation of chemokine production / negative regulation of canonical NF-kappaB signal transduction / positive regulation of phagocytosis / positive regulation of defense response to virus by host / tumor necrosis factor-mediated signaling pathway / activation of innate immune response / positive regulation of interleukin-1 beta production / regulation of autophagy / positive regulation of interleukin-8 production / positive regulation of JNK cascade / NOD1/2 Signaling Pathway / regulation of protein stability / protein homooligomerization / kinase binding / positive regulation of DNA-binding transcription factor activity / cellular response to type II interferon / positive regulation of inflammatory response / positive regulation of non-canonical NF-kappaB signal transduction / cellular response to mechanical stimulus / activation of cysteine-type endopeptidase activity involved in apoptotic process / SARS-CoV-1 activates/modulates innate immune responses / positive regulation of interleukin-6 production / positive regulation of tumor necrosis factor production / azurophil granule lumen / positive regulation of type II interferon production / positive regulation of T cell activation / cellular response to tumor necrosis factor / positive regulation of NF-kappaB transcription factor activity / regulation of inflammatory response / cellular response to lipopolysaccharide / regulation of apoptotic process / secretory granule lumen / positive regulation of canonical NF-kappaB signal transduction / defense response to virus / microtubule / defense response to Gram-negative bacterium / endopeptidase activity / protease binding Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | ||||||
Authors | Hollingsworth, L.R. / David, L. / Li, Y. / Ruan, J. / Wu, H. | ||||||
Funding support | United States, 1items
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Citation | Journal: Nat Commun / Year: 2021 Title: Mechanism of filament formation in UPA-promoted CARD8 and NLRP1 inflammasomes. Authors: L Robert Hollingsworth / Liron David / Yang Li / Andrew R Griswold / Jianbin Ruan / Humayun Sharif / Pietro Fontana / Elizabeth L Orth-He / Tian-Min Fu / Daniel A Bachovchin / Hao Wu / Abstract: NLRP1 and CARD8 are related cytosolic sensors that upon activation form supramolecular signalling complexes known as canonical inflammasomes, resulting in caspase-1 activation, cytokine maturation ...NLRP1 and CARD8 are related cytosolic sensors that upon activation form supramolecular signalling complexes known as canonical inflammasomes, resulting in caspase-1 activation, cytokine maturation and/or pyroptotic cell death. NLRP1 and CARD8 use their C-terminal (CT) fragments containing a caspase recruitment domain (CARD) and the UPA (conserved in UNC5, PIDD, and ankyrins) subdomain for self-oligomerization, which in turn form the platform to recruit the inflammasome adaptor ASC (apoptosis-associated speck-like protein containing a CARD) or caspase-1, respectively. Here, we report cryo-EM structures of NLRP1-CT and CARD8-CT assemblies, in which the respective CARDs form central helical filaments that are promoted by oligomerized, but flexibly linked, UPAs surrounding the filaments. Through biochemical and cellular approaches, we demonstrate that the UPA itself reduces the threshold needed for NLRP1-CT and CARD8-CT filament formation and signalling. Structural analyses provide insights on the mode of ASC recruitment by NLRP1-CT and the contrasting direct recruitment of caspase-1 by CARD8-CT. We also discover that subunits in the central NLRP1 filament dimerize with additional exterior CARDs, which roughly doubles its thickness and is unique among all known CARD filaments. Finally, we engineer and determine the structure of an ASC-caspase-1 octamer, which suggests that ASC uses opposing surfaces for NLRP1, versus caspase-1, recruitment. Together these structures capture the architecture and specificity of the active NLRP1 and CARD8 inflammasomes in addition to key heteromeric CARD-CARD interactions governing inflammasome signalling. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7keu.cif.gz | 137.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7keu.ent.gz | 105.9 KB | Display | PDB format |
PDBx/mmJSON format | 7keu.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7keu_validation.pdf.gz | 771.4 KB | Display | wwPDB validaton report |
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Full document | 7keu_full_validation.pdf.gz | 806.4 KB | Display | |
Data in XML | 7keu_validation.xml.gz | 31.1 KB | Display | |
Data in CIF | 7keu_validation.cif.gz | 45.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ke/7keu ftp://data.pdbj.org/pub/pdb/validation_reports/ke/7keu | HTTPS FTP |
-Related structure data
Related structure data | 22233MC 6xkjC 6xkkC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | |
EM raw data | EMPIAR-10566 (Title: ASC-CARD:Caspase-1-CARD octamer / Data size: 1.2 TB Data #1: Unaligned multi-frame micrographs for the ASC-CASP1 CARD octamer [micrographs - multiframe]) |
-Links
-Assembly
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: _ / Refine code: _
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